Prvolinijsko liječenje uznapredovalog raka jajnika: novosti

Ovarian cancer is the fifth most common cause of death among malignant diseases in women in Europe. The standard treatment is cytoreductive surgery, followed by platinum-taxane based chemotherapy. In patients with advanced disease, a valid option is a neoadjuvant chemotherapy followed by interval debulking surgery. Despite the progress in primary treatment, almost 70% of the patients relapse. There is a significant need for better first-line treatment to avoid or delay relapse and improve ovarian cancer outcomes. The most significant change involves the changes in the treatment schedule and new drugs in first-line chemotherapy. Bevacizumab is approved in first-line treatment combined with carboplatin and paclitaxel as it improves progression-free survival (PFS) in patients with a higher risk of recurrence. After achieving the response to first-line chemotherapy, maintenance therapy with poly-adenosine-diphosphate-ribose-polymerase (PARP) inhibitors prolongs PFS in patients with homologous recombination deficiency (HRD). Patients with BRCA mutations obtain the most significant benefit.Rak jajnika je peti najčešći uzrok smrti među zloćudnim bolestima kod žena u Europi. Standardni način liječenja je primarna citoredukcija praćena kemoterapijom temeljenom na platini i taksanima. Kod bolesnica s uznapredovalom bolesti jedna od opcija liječenja je neoadjuvantna kemoterapija s intervalnom citoredukcijom. Unatoč napretku u liječenju, gotovo 70% bolesnica razvije povrat bolesti. Postoji značajna potreba za poboljšanjem prvolinijskog liječenja s ciljem izbjegavanja ili odgađanja povrata bolesti i poboljšanja ishoda liječenja bolesnica s rakom jajnika. Najvažnija promjena uključuje izmjene u načinu primjene lijekova i dodavanje novih lijekova prvolinijskoj kemoterapiji. Bevacizumab je odobren u prvolinijskom liječenju u kombinaciji s karboplatinom i paklitakselom zbog poboljšanja preživljenja do napredovanja bolesti (PFS) kod bolesnica s povećanim rizikom od recidiva. Terapija održavanja PARP inhibitorima, nakon odgovora na prvolinijsku kemoterapiju, produljuje PFS kod bolesnica s poremećajem u sustavu popravka dvostrukih lomova deoksiribonukleinske kiseline homolognom rekombinacijom. Najveću korist imaju bolesnice s BRCA mutacijama

Terapijski pristup seroznom karcinomu jajnika niskog gradusa

Low-grade serous ovarian cancer (LGSOC) has less aggressive behavior and a better clinical outcome than high-grade serous ovarian cancer (HGSOC). Considering that this malignancy is relatively chemoresistant, surgery is the keystone of treatment, with a strong recommendation for maximal cytoreduction. Women with stage IA-IB disease should undergo observation alone after primary cytoreductive surgery. In contrast, observation, chemotherapy, or endocrine therapy are possible options for those with stage IC-IIA disease. Patients with stage IIB-IV disease receive either chemotherapy with carboplatin and paclitaxel for six cycles followed by endocrine therapy, most commonly with aromatase inhibitors, or endocrine therapy alone until disease progression or unacceptable toxicity. Surgery, chemotherapy, and endocrine therapy are also used in patients with recurrent disease. Targeted agents, especially mitogen-activated protein kinase (MEK) inhibitors and cyclin-dependent kinase (CDK) inhibitors, are currently under evaluation in this clinical setting. Additional research on the genomics of LGSOC to better define the activating gene mutations involved in the carcinogenesis is strongly warranted to improve the prognosis with this malignancy.Niskogradusni serozni karcinom jajnika (LGSOC) manje je agresivan i ima bolji klinički ishod u usporedbi s visokogradusnim seroznim karcinomom jajnika (HGSOC). Kirurško liječenje s pokušajem maksimalne citoredukcije važno je i opravdano zbog relativne kemorezistencije ovog tumora. Stadije bolesti IA-IB trebalo bi klinički pratiti nakon primarne citoredukcije, dok su kliničko praćenje, kemoterapija ili hormonska terapija predložene mogućnosti za stadije bolesti IC-IIA. Bolesnice stadija IIB-IV liječe se kemoterapijom sastavljenom od karboplatina i paklitaksela tijekom 6 ciklusa koju slijedi hormonska terapija, najčešće inhibitorima aromataze, ili pak samom hormonskom terapijom do progresije bolesti ili neprihvatljive toksičnosti. Kirurško liječenje, kemoterapija i hormonska terapija također se koriste za bolesnice s povratom bolesti. U tijeku su klinička istraživanja ciljanom terapijom, posebno s inhibitorima mitogenom-aktiviranih proteinskih kinaza (MEK) i inhibitorima kinaza ovisnih o ciklinu (CDK). Dodatna istraživanja genomike LGSOC-a, u cilju boljeg definiranja aktivacije genskih mutacija uključenih u karcinogenezu, neophodna su radi poboljšanja prognoze ove zloćudne bolesti

Ovarian Cancer

Karcinom jajnika glavni je uzrok smrtnosti među karcinomima ženskoga spolnog sustava. Ne postoje rutinski testovi rane dijagnostike raka jajnika, a rano prepoznavanje bolesti otežano je zbog oskudne simptomatologije. Ukupna stopa preživljenja bolesnica od karcinoma jajnika iznosi gotovo 50%, što je velik napredak u odnosu na rane 80-e godine kada je iznosila oko 35%, a može se zahvaliti uvođenju paklitaksela u liječenje.Ovarian cancer is the main reason of death among gynecological cancers. There is no routine test for early diagnosis of ovarian cancer and early detection of this cancer is difficult because of lack of simptomatology. Overall survival rate among patients with ovarian cancer is almost 50 % and it represents a significant increase of survival in the last decade due the introduction of paclitaxel in the treatment of advanced stages of ovarian carcinoma

Role of CDK4/6 inhibitors in metastatic hormon positive HER2 negative breast cancer treatment

Primjena inhibitora CDK4/6 u liječenju hormonski ovisnoga metastatskog raka dojke negativnog na HER-2 dovela je do bitnog poboljšanja kontrole bolesti, i to ponajprije znatnim produljenjem preživljenja bez progresije bolesti, uz prihvatljiv profil toksičnosti. Osnovno djelovanje inhibitora CDK4/6 jest odgađanje razvoja rezistencije na endokrinu terapiju, odnosno reverziju već nastale rezistencije. Medijani preživljenja bez progresije bolesti kreću se oko 20 i više mjeseci u prvoj liniji liječenja i 10-ak mjeseci i više u drugoj liniji. U prvoj liniji liječenja kombinirani su s aromataznim inhibitorima, a u drugoj s fulvestrantom. Produljenjem vremena bez napredovanja bolesti odgađa se primjena kemoterapije, a bolesnicama se osigurava bolja kvaliteta života. Zbog svega navedenoga ovi lijekovi u kombinaciji s endokrinom terapijom nova su, visokovrijedna terapijska opcija u liječenju metastatskog raka dojke. Međutim, ostaju brojna otvorena pitanja za svakodnevnu kliničku praksu kao što su optimalan odabir bolesnica za prvolinijsko i drugolinijsko liječenje, sekvenciranje drugih lijekova nakon progresije bolesti na inhibitore CDK4/6 te dostupnost i cijena liječenja.Implementation of CDK4/6 inhibitors in metastatic hormone receptor positive, HER2 negative breast cancer treatment significantly improves progression free survival. CDK4/6 inhibitors are characterized by favorable toxicity profile. CDK4/6 inhibitor administration delays and/or overcomes endocrine therapy resistance in metastatic breast cancer. CDK4/6 inhibitors were tested in both first line treatment in combination with aromatase inhibitors, and in second line treatment in combination with fulvestrant. Progression free survival longer than 20 months in the first and longer than 10 months in the second treatment line has been achieved. Progression free survival prolongation may delay chemotherapy administration and consequently enable longer period with maintained quality of life. CDK4/6 inhibitors in combination with endocrine therapy represent a new valuable treatment option for metastatic hormone receptor positive HER2 negative breast cancer. However , many questions such as optimal patient selection as well as positioning of the CDK4/6 inhibitors and other endocrine therapy options during the course of metastatic disease treatment, remain unanswered. Furthermore, availability and cost of CDK4/6 inhibitors are also important issues

Ovarian Cancer

Karcinom jajnika glavni je uzrok smrtnosti među karcinomima ženskoga spolnog sustava. Ne postoje rutinski testovi rane dijagnostike raka jajnika, a rano prepoznavanje bolesti otežano je zbog oskudne simptomatologije. Ukupna stopa preživljenja bolesnica od karcinoma jajnika iznosi gotovo 50%, što je velik napredak u odnosu na rane 80-e godine kada je iznosila oko 35%, a može se zahvaliti uvođenju paklitaksela u liječenje.Ovarian cancer is the main reason of death among gynecological cancers. There is no routine test for early diagnosis of ovarian cancer and early detection of this cancer is difficult because of lack of simptomatology. Overall survival rate among patients with ovarian cancer is almost 50 % and it represents a significant increase of survival in the last decade due the introduction of paclitaxel in the treatment of advanced stages of ovarian carcinoma

Nasljedni karcinom dojke i jajnika - iskustva Kliničkog bolničkog centra Split

Aim: To investigate the clinical and pathohistological tumor characteristics, treatment, and treatment outcomes in patients with hereditary breast and ovarian cancer who were diagnosed, treated, and monitored at the University Hospital of Split from October 1999 to April 2021. Methods: The data were collected retrospectively from the medical history of 15 patients. They included the patient’s age at diagnosis, family history of malignancies, histological subtype, grade, breast cancer immunophenotype, stage of disease, status and types of BRCA mutations, type of surgical and oncological treatment, the specifics of metachronous bilateral breast cancers, the specifics of synchronous breast and ovarian cancers, and the outcome of treatment through overall survival (OS). Results: The median age of patients at the time of diagnosis of breast cancer was 53 years, and for ovarian cancer it was 56 years. A positive family history was confirmed in 13 patients (87%). All ovarian cancer patients had a high-grade serous histologic type, most often diagnosed in FIGO stages III and IV. Breast cancers were most commonly diagnosed in stages IA and IIA, with equally represented triple-negative and luminal immunophenotypes. The most common mutation was BRCA1 c.5266dup. The median OS of our patients was not reached. Conclusion: The clinical features of patients, pathohistological characteristics of tumors, and treatment outcomes in our study population are comparable with reports in the literature, respecting the specifics of different nations and races.Cilj: Istražiti kliničke osobitosti, patohistološke karakteristike tumora, način i ishode liječenja bolesnica s nasljednim karcinomom dojke i jajnika koje su dijagnosticirane, liječene i praćene u Kliničkom bolničkom centru Split od listopada 1999. do travnja 2021. godine. Metode: Podatci su prikupljeni retrospektivno iz povijesti bolesti 15 bolesnica. Uključivali su dob bolesnica kod dijagnoze bolesti, obiteljsku anamnezu za zloćudne bolesti, histološki podtip, gradus, imunofenotip karcinoma dojke, stadij bolesti, status i tip BRCA mutacija, osobitosti kirurškog i onkološkog liječenja, specifičnosti metakrono nastalih bilateralnih karcinoma dojke, specifičnosti sinkrono nastalih karcinoma dojke i jajnika te ishod liječenja kroz ukupno preživljenje. Rezultati: Medijan dobi bolesnica u trenutku dijagnoze raka dojke bio je 53 godine, a za karcinom jajnika 56 godina. Pozitivna obiteljska anamneza potvrđena je u 13 (87%) bolesnica. Karcinom jajnika je kod svih bolesnica bio seroznog papilarnog histološkog podtipa visokog gradusa i najčešće dijagnosticiran u FIGO stadiju III i IV. Karcinom dojke je najčešće dijagnosticiran u stadiju IA i IIA, jednake zastupljenosti trostruko negativnog i luminalnog imunofenotipa. Najčešća mutacija je bila BRCA1 c.5266dup. Medijan ukupnog preživljenja naših bolesnica nije dosegnut. Zaključak: Kliničke osobitosti bolesnica, patohistološke karakteristike tumora kao i ishodi liječenja u našoj studijskoj populaciji su usporedivi s izvješćima iz literature, respektirajući specifičnosti različitih naroda i rasa

Kliničke preporuke za dijagnozu, liječenje i praćenje bolesnika oboljelih od raka nepoznata primarnog podrijetla [Clinical recommendations for diagnosis, treatment and monitoring of patients with cancer of unknown primary site]

Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia

CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH CANCER OF UNKNOWN PRIMARY SITE

Rak nepoznata primarnog podrijetla obuhvaća vrlo heterogenu skupinu različitih malignih tumora koji se prezentiraju u metastatskoj fazi bolesti. Dijagnoza se postavlja na temelju patohistološke potvrde maligne bolesti uz nemogućnost dokaza postojanja primarnog tumora nijednom dostupnom dijagnostičkom metodom. Iako je općenito loše prognoze, prepoznati su prognostički povoljni klinički entiteti koji čine temeljnu skupinu bolesnika za aktivno onkološko liječenje. U tekstu koji slijedi sadržane su kliničke upute s ciljem standardizacije dijagnostičkih postupaka, liječenja i praćenja bolesnika s nepoznatim primarnim rakom u Republici Hrvatskoj.Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia

Kliničke preporuke za dijagnozu, liječenje i praćenje bolesnika oboljelih od raka nepoznata primarnog podrijetla [Clinical recommendations for diagnosis, treatment and monitoring of patients with cancer of unknown primary site]

Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia

CLINICAL RECOMMENDATIONS FOR DIAGNOSIS, TREATMENT AND MONITORING OF PATIENTS WITH CANCER OF UNKNOWN PRIMARY SITE

Rak nepoznata primarnog podrijetla obuhvaća vrlo heterogenu skupinu različitih malignih tumora koji se prezentiraju u metastatskoj fazi bolesti. Dijagnoza se postavlja na temelju patohistološke potvrde maligne bolesti uz nemogućnost dokaza postojanja primarnog tumora nijednom dostupnom dijagnostičkom metodom. Iako je općenito loše prognoze, prepoznati su prognostički povoljni klinički entiteti koji čine temeljnu skupinu bolesnika za aktivno onkološko liječenje. U tekstu koji slijedi sadržane su kliničke upute s ciljem standardizacije dijagnostičkih postupaka, liječenja i praćenja bolesnika s nepoznatim primarnim rakom u Republici Hrvatskoj.Cancer of unknown primary (CUP) site comprises very heterogeneous group of various malignant tumors presented in metastatic phase of the disease. Diagnosis is set when primary site remains unidentified after a thorough diagnostic evaluation in patients with histologically proven malignant metastatic disease. Despite poor prognosis in most patients, favorable prognostic clinical entities have been recognized constituting the most important group of patients for oncological treatment. The following text presents the clinical guidelines in order to standardize the diagnosis, treatment and follow-up of patients with cancer of unknown primary site in the Republic of Croatia